Antibiotic resistance poses a serious challenge to infectious disease control. Vancomycin is an antibiotic that has been used to treat infections caused by opportunistic Gram-positive bacteria including Enterococcus species and methicillin-resistant Staphylococcus aureus. However, the emergence of vancomycin resistance has made it increasingly difficult to treat these types of infections.
The enzymes responsible for vancomycin resistance are encoded in genetic material called operons. Specific proteins known as VanR or VanU regulators control the transcription of these operons. VanU is able to bind at two distinct and non-related locations found on one particular operon called the VanG operon. This operon is associated with vancomycin resistance. This bi-locational mode of gene regulation is of interest in understanding the mechanism of vancomycin resistance.
A team at the University of Toronto working with the Center for Structural Genomics of Infectious Diseases has used x-ray crystallography to determine the 3D structure of VanU to high resolution (1.12 Å). The structure reveals a dimer—a compound made of two protein subunits —with the helix-turn-helix fold, a common configuration, or DNA binding motif, in bacteria. The orientation of the DNA recognition helices suggests the VanU dimer is able to bend DNA in its mechanism of transcription regulation.
For more information, please see IDP91041 or Protein Data Bank entries 3T75 and 3T76.
All featured structures from the NIAID Structural Genomics Centers
Last Updated September 02, 2011